**1. Introduction**

The human microbiota, now considered as a functional organ in se, consists of a complex community of microorganisms (bacteria, yeasts, fungi, archea, protozoa and virus), living on our skin and mucosal tissues, hence forming an efficient ecosystem with the body [1,2].

Despite the apparent alliance between gu<sup>t</sup> microbiota and its host, this intimate relationship poses a permanent threat to the host's health, requiring constant control. Thus, the role of the human immune system in fine-tuning and shaping the microbiota is of paramount importance [3].

The function of microbiota can be further extrapolated and considered beneficial or pathological beyond the gastrointestinal (GI) tract, for example in the liver. In fact, venous blood flow from the gu<sup>t</sup> reaches the liver via the portal vein, carrying microbial products and inducing the host's immunological responses to these. On the other hand, the liver produces bile that flows to the gu<sup>t</sup> directly and influences the resident microbial environment [4]. This circulatory loop between liver and gu<sup>t</sup> is an explicative tale of how changes in the gu<sup>t</sup> flora can have both beneficial and/or harmful consequences for the host [5].

This review summarizes the evidences on the triangular interaction between gu<sup>t</sup> microbiota, immune system and liver, in health and disease. Since the epidemiology of chronic liver diseases is changing, due to the decreasing rate of viral hepatitis and the increasing new epidemic of a wide spectrum of alcoholic and non-alcoholic fatty liver disease (NAFLD) [6,7], we focus our attention on non-viral hepatitis. Furthermore, due to the link reported between severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection and hepatic dysfunctions, we outline the emerging role of the gu<sup>t</sup> virome in liver diseases.
